Summary Studies during this year focused on the role of BIG1 and BIG2 on the regulation of signal transduction and regulatory pathways, focusing the potential importance of the AKAP domains, cyclic AMP-dependent as well as other protein kinases and protein phosphatases. These studies are being continued in association with my long-time collaborator, Joel Moss. Significance BIG1 and BIG2, guanine nucleotide-exchange factors (GEFs) activate Arfs by accelerating replacement of bound GDP with GTP and contain one or more AKAP sequences that scaffold multimolecular assemblies to limit cAMP signaling in space and time. Beta-catenin was among HeLa cell proteins co-immunoprecipitated with BIG1 or BIG2, and direct or indirect interactions, respectively, were demonstrated. Current studies are directed at defining other pathways regulated by BIG1 and BIG2 through their Sec7 guanine nucleotide-binding domains or through their AKAP domains. It appears that BIG1 and BIG2 are widely distributed in cells and function in variety of different pathways, depending on the proteins involved in their complexes.